Histological assessment of granuloma formation for the management of cutaneous <i>Mycobacterium chelonae</i> infection

Mycobacterium chelonae potentially causes skin infection.1 Representative histopathological findings of this infection include vacuoles and epithelioid granuloma.2 In this study, four cases of cutaneous M. chelonae infection with distinct clinicopathological findings are presented. A literature review was conducted to clarify its clinicopathological characteristics. A 70-year-old female with interstitial pneumonia on oral prednisolone (PSL) treatment presented with multiple ulcers and nodules on her leg (Figure 1a). A skin biopsy taken from an ulcerated nodule revealed dermal neutrophilic infiltration with vacuoles (Figure 1b). Mycobacteria were detected within the vacuoles by Ziehl–Neelsen staining (Figure 1c). M. chelonae was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A 6-month administration of clarithromycin (CAM), amikacin and doxycycline was effective. A 74-year-old male with diabetes mellitus presented with erythema on the arm (Figure 1d). A skin biopsy detected dermal granuloma with neutrophils (Figure 1e,f). Acid-fast bacilli (AFB) was not observed. M. chelonae was detected in the tissue culture. Six-month CAM monotherapy and thermal therapy were successful. A 57-year-old male with dermatomyositis on oral PSL treatment had been diagnosed with disseminated M. chelonae infection by swab culture (Figure 1g-i). Multiple drug therapies were initiated but eventually discontinued due to appetite loss and thrombocytopenia. The patient died 4 months after the admission. The last case was a 64-year-old male with ulcerative colitis administrated oral hydrocortisone presented with a nodule on the thigh (Figure S1). M. chelonae was detected from the culture of drained discharge. The nodule regressed a week after drainage. The literature review found 43 histologically granuloma-present and 24 granuloma-absent cutaneous M. chelonae infectees in the last decade. Ulcer was infrequently observed in the former (27.9%) compared to the latter group (54.2%) (p < 0.05; Table S1). When compared to the granuloma absent group, AFB was less frequently detected in the granuloma-present group (87.5% vs. 55.8%) with lower incidence of ulcer formation, suggesting that these patients had more intense immune reaction analogous to tuberculous and tuberculoid leprosy.3 The incidence of granuloma was not different regarding the duration from onset to biopsy or biopsy sites. The current analysis suggests that ulcers or surrounding areas are preferential biopsy sites for successful identification of M. chelonae, as such clinical manifestation may suggest the presence of histological vacuoles containing the bacilli in the granuloma-absent type. For the cases without ulcer formation, well-coordinated sampling strategies collecting various diagnostic materials would enable early diagnosis and initiation of appropriate treatments. Combination therapies including CAM have been preferable to prevent drug resistance,4 and therefore highly recommended for granuloma-absent patients. It should be noted, however, that more than 10% of reported cases require switching of medications due to adverse events.1, 5 Minimization of the length of intervention would be possible by the addition of surgical interventions or thermal therapy. In aggregate, these findings support the importance of fit-for-purpose site selection of biopsy sites based on histopathological characteristics to improve therapeutic outcomes of cutaneous M. chelonae infection. None. None declared. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.